Single-shot echo-planar imaging (ss-EPI) has limited application in vertebral column imaging due to numerous artifacts. Therefore, we aimed to compare readout-segmented echo-planar imaging (rs-EPI) to ss-EPI and assess its value in the differential diagnosis of vertebral infectious, tumoral infiltrative, and degenerative disorders. Sixty-six adult patients with spondylodiscitis (SD, n = 26), tumoral infiltration (TI, n = 20), or Modic type I degeneration (DE, n = 20) findings on spinal magnetic resonance imaging (MRI) included in this retrospective study. Two radiologists scored images for quality on a 4-point scale (image resolution, degree of geometric distortion, lesion selectivity, and diagnostic reliability) and measured signal intensity (SI), apparent diffusion coefficient (ADC), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). DE and SD groups also united to form the benign group. In all groups, rs-EPI performed better than ss-EPI in image quality, SNR, and CNR (p < .05). The difference between mean pathological ADC (ADCP) in the two sequences was statistically significant (p < .05). There was no significant difference between the groups in terms of ADCP in rs-EPI (p = .229), unlike ss-EPI (p = .025). Pathological SI (SIP) and CNR in rs-EPI were significantly higher in the malignant group than benign group (p = .002, p < .001). In rs-EPI, no significant difference was found between malignant and benign groups' ADCP (p = .13). The rs-EPI is a diffusion-weighted imaging (DWI) method with higher image quality that diminishes motion-induced phase errors and increases resolution through phase corrections. However, the distinction of malignant and benign vertebral bone marrow pathologies is unsatisfactory for rs-EPI compared with ss-EPI.